P. falciparum infection durations and infectiousness are shaped by antigenic variation and innate and adaptive host immunity in a mathematical model.
P. falciparum infection durations and infectiousness are shaped by antigenic variation and innate and adaptive host immunity in a mathematical model.
复制标题
DOI：
10.1371/journal.pone.0044950
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Eckhoff P
中科院分区：
文献类型：
--
作者：
Eckhoff P
关于恶性疟原虫宿主内动力学、免疫力和传播的问题仍然存在许多问题，这些问题可能影响公共卫生运动的规划。这些知识差距涉及疟疾感染持续时间的分布、急性感染期间寄生虫血症高峰的确定、配子体与免疫反应和对蚊子的感染性之间的关系以及抗原结构对再感染结果的影响。恶性疟原虫宿主内动态的本模型实现了寄生虫和免疫动态的详细表示，其结构基于其基础中的第一原理生物学的最小外推。该模型的目的是快速，方便地适应增益的机械理解，并通过计算机实验来评估替代生物学假设的影响。模拟跟踪寄生虫从肝脏阶段通过详细的无性生殖周期清除，同时跟踪配子体种群。模型化的免疫系统包括先天性炎症和对抗原库的特异性抗体应答。机制的重点提供了明确的解释，通过抗原变异和先天性和适应性免疫的相互作用，感染持续时间的分布结构。对蚊子的抵抗力似乎不仅由配子体的密度决定，而且还由炎性细胞因子的水平决定，这与广泛的一系列研究结果相一致。最后，预先存在的免疫力可以减少或增加再感染时的感染持续时间，这取决于抗原库的重叠程度和预先存在的免疫力的强度。
Many questions remain about P. falciparum within-host dynamics, immunity, and transmission–issues that may affect public health campaign planning. These gaps in knowledge concern the distribution of durations of malaria infections, determination of peak parasitemia during acute infection, the relationships among gametocytes and immune responses and infectiousness to mosquitoes, and the effect of antigenic structure on reinfection outcomes. The present model of intra-host dynamics of P. falciparum implements detailed representations of parasite and immune dynamics, with structures based on minimal extrapolations from first-principles biology in its foundations. The model is designed to quickly and readily accommodate gains in mechanistic understanding and to evaluate effects of alternative biological hypothesis through in silico experiments. Simulations follow the parasite from the liver-stage through the detailed asexual cycle to clearance while tracking gametocyte populations. The modeled immune system includes innate inflammatory and specific antibody responses to a repertoire of antigens. The mechanistic focus provides clear explanations for the structure of the distribution of infection durations through the interaction of antigenic variation and innate and adaptive immunity. Infectiousness to mosquitoes appears to be determined not only by the density of gametocytes but also by the level of inflammatory cytokines, which harmonizes an extensive series of study results. Finally, pre-existing immunity can either decrease or increase the duration of infections upon reinfection, depending on the degree of overlap in antigenic repertoires and the strength of the pre-existing immunity.
登录
查看更多内容
影响因子：
82.9
作者：
通讯作者：
--
Toll样受体9介导疟疾色素血液唑素的先天免疫激活。
DOI：
10.1084/jem.20041836
发表时间：
2005-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coban C;Ishii KJ;Kawai T;Hemmi H;Sato S;Uematsu S;Yamamoto M;Takeuchi O;Itagaki S;Kumar N;Horii T;Akira S
通讯作者：
Akira S
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
DOI：
10.1084/jem.172.1.379
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blackman MJ;Heidrich HG;Donachie S;McBride JS;Holder AA
通讯作者：
Holder AA
DOI：
10.4269/tropmed.1999.61-044
发表时间：
1999-07-01
影响因子：
3.3
作者：
Collins, WE;Jeffery, GM
通讯作者：
Jeffery, GM